金黄色葡萄球菌β毒素的结构与生物学活性
Structure and biological activities of beta toxin from Staphylococcus aureus.
作者信息
Huseby Medora, Shi Ke, Brown C Kent, Digre Jeff, Mengistu Fikre, Seo Keun Seok, Bohach Gregory A, Schlievert Patrick M, Ohlendorf Douglas H, Earhart Cathleen A
机构信息
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
出版信息
J Bacteriol. 2007 Dec;189(23):8719-26. doi: 10.1128/JB.00741-07. Epub 2007 Sep 14.
Beta toxin is a neutral sphingomyelinase secreted by certain strains of Staphylococcus aureus. This virulence factor lyses erythrocytes in order to evade the host immune system as well as scavenge nutrients. The structure of beta toxin was determined at 2.4-A resolution using crystals that were merohedrally twinned. This structure is similar to that of the sphingomyelinases of Listeria ivanovii and Bacillus cereus. Beta toxin belongs to the DNase I folding superfamily; in addition to sphingomyelinases, the proteins most structurally related to beta toxin include human endonuclease HAP1, Escherichia coli endonuclease III, bovine pancreatic DNase I, and the endonuclease domain of TRAS1 from Bombyx mori. Our biological assays demonstrated for the first time that beta toxin kills proliferating human lymphocytes. Structure-directed active site mutations show that biological activities, including hemolysis and lymphotoxicity, are due to the sphingomyelinase activity of the enzyme.
β毒素是由某些金黄色葡萄球菌菌株分泌的一种中性鞘磷脂酶。这种毒力因子可裂解红细胞，以逃避宿主免疫系统并获取营养。利用呈缺面体孪晶的晶体，以2.4埃的分辨率确定了β毒素的结构。该结构与伊氏李斯特菌和蜡样芽孢杆菌的鞘磷脂酶结构相似。β毒素属于DNA酶I折叠超家族；除了鞘磷脂酶外，在结构上与β毒素关系最密切的蛋白质包括人核酸内切酶HAP1、大肠杆菌核酸内切酶III、牛胰DNA酶I以及家蚕TRAS1的核酸内切酶结构域。我们的生物学试验首次证明β毒素可杀死增殖的人类淋巴细胞。基于结构的活性位点突变表明，包括溶血和淋巴毒性在内的生物学活性是由于该酶的鞘磷脂酶活性所致。
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